Mount Sinai Researchers Identify Protein That Keeps Blood Stem Cells Healthy as They Age
Early Findings May Help to Reduce Risk of Age-Related Blood Cancers
A protein may be the key to maintaining the health of aging blood stem cells, according to work by researchers at the Icahn School of Medicine at Mount Sinai recently published online in Stem Cell Reports. Human adults keep stem cell pools on hand in key tissues, including the blood. These stem cells can become replacement cells for those lost to wear and tear. But as the blood stem cells age, their ability to regenerate blood declines, potentially contributing to anemia and the risk of cancers like acute myeloid leukemia and immune deficiency. Whether this age-related decline in stem cell health is at the root of overall aging is unclear.
The new Mount Sinai study reveals how loss of a protein called Sirtuin1 (SIRT1) affects the ability of blood stem cells to regenerate normally, at least in mouse models of human disease. This study has shown that young blood stem cells that lack SIRT1 behave like old ones. With use of advanced mouse models, she and her team found that blood stem cells without adequate SIRT1 resembled aged and defective stem cells, which are thought to be linked to development of malignancies.
"Our data shows that SIRT1 is a protein that is required to maintain the health of blood stem cells and supports the possibility that reduced function of this protein with age may compromise healthy aging," says Saghi Ghaffari, MD, PhD, Associate Professor of Developmental and Regenerative Biology at Mount Sinai's Black Family Stem Cell Institute, Icahn School of Medicine. "Further studies in the laboratory could improve are understanding between aging stem cells and disease."
Next for the team, which includes Pauline Rimmelé, PhD, is to investigate whether or not increasing SIRT1 levels in blood stem cells protects them from unhealthy aging or rejuvenates old blood stem cells. The investigators also plan to look at whether SIRT1 therapy could treat diseases already linked to aging, faulty blood stem cells.
They also believe that SIRT1 might be important to maintaining the health of other types of stem cells in the body, which may be linked to overall aging.
The notion that SIRT1 is a powerful regulator of aging has been highly debated, but its connection to the health of blood stem cells "is now clear," says Dr. Ghaffari. "Identifying regulators of stem cell aging is of major significance for public health because of their potential power to promote healthy aging and provide targets to combat diseases of aging," Dr. Ghaffari says.
Researchers from Harvard Medical School and Children's Hospital in Boston participated in the study.
About the Mount Sinai Health System
The Mount Sinai Health System is New York City's largest academic medical system, encompassing eight hospitals, a leading medical school, and a vast network of ambulatory practices throughout the greater New York region. Mount Sinai advances medicine and health through unrivaled education and translational research and discovery to deliver care that is the safest, highest-quality, most accessible and equitable, and the best value of any health system in the nation. The Health System includes approximately 7,300 primary and specialty care physicians; 13 joint-venture ambulatory surgery centers; more than 415 ambulatory practices throughout the five boroughs of New York City, Westchester, Long Island, and Florida; and more than 30 affiliated community health centers. The Mount Sinai Hospital is ranked on U.S. News & World Report's "Honor Roll" of the top 20 U.S. hospitals and is top in the nation by specialty: No. 1 in Geriatrics and top 20 in Cardiology/Heart Surgery, Diabetes/Endocrinology, Gastroenterology/GI Surgery, Neurology/Neurosurgery, Orthopedics, Pulmonology/Lung Surgery, Rehabilitation, and Urology. New York Eye and Ear Infirmary of Mount Sinai is ranked No. 12 in Ophthalmology. Mount Sinai Kravis Children's Hospital is ranked in U.S. News & World Report’s “Best Children’s Hospitals” among the country’s best in four out of 10 pediatric specialties. The Icahn School of Medicine is one of three medical schools that have earned distinction by multiple indicators: ranked in the top 20 by U.S. News & World Report's "Best Medical Schools," aligned with a U.S. News & World Report "Honor Roll" Hospital, and No. 14 in the nation for National Institutes of Health funding. Newsweek’s “The World’s Best Smart Hospitals” ranks The Mount Sinai Hospital as No. 1 in New York and in the top five globally, and Mount Sinai Morningside in the top 20 globally.